Synaptic targeting of the postsynaptic density protein PSD-95 mediated by lipid and protein motifs
Synaptic targeting of the postsynaptic density protein PSD-95 mediated by lipid and protein motifs
复制标题
DOI：
10.1016/s0896-6273(00)80705-9
复制
发表时间：
1999-03-01
期刊：
影响因子：
16.2
通讯作者：
Bredt, DS
中科院分区：
文献类型：
--
作者：
Craven, SE;El-Husseini, AE;Bredt, DS
在突触发育过程中，蛋白质聚集在特定的突触前和突触后结构上。在这些位点介导蛋白质聚集的机制尚不清楚。为了研究这一过程，我们在培养的海马神经元中表达绿色荧光蛋白- (GFP-)标记的PSD-95，分析了突触后密度蛋白PSD-95的突触靶向性。我们发现突触后聚类依赖于PSD-95的三个要素：n端棕榈酰化，前两个PDZ结构域和c端靶向基序。相反，PDZ3、SH3或鸟苷酸激酶（GK）结构域的破坏不影响突触靶向。棕榈酰化足以将弥漫表达的SAP-97靶向到突触，并且棕榈酰化不能被替代的膜关联基元所取代，这表明一个特殊的突触脂质环境介导了突触后聚集。PSD-95对PDZ结构域和c端结构域的要求表明，蛋白-蛋白相互作用与脂质相互作用在突触靶向中协同作用。
During synaptic development, proteins aggregate at specialized pre- and postsynaptic structures. Mechanisms that mediate protein clustering at these sites remain unknown. To investigate this process, we analyzed synaptic targeting of a postsynaptic density protein, PSD-95, by expressing green fluorescent protein- (GFP-) tagged PSD-95 in cultured hippocampal neurons. We find that postsynaptic clustering relies on three elements of PSD-95: N-terminal palmitoylation, the first two PDZ domains, and a C-terminal targeting motif. In contrast, disruptions of PDZ3, SH3, or guanylate kinase (GK) domains do not affect synaptic targeting. Palmitoylation is sufficient to target the diffusely expressed SAP-97 to synapses, and palmitoylation cannot be replaced with alternative membrane association motifs, suggesting that a specialized synaptic lipid environment mediates postsynaptic clustering. The requirements for PDZ domains and a C-terminal domain of PSD-95 indicate that protein-protein interactions cooperate with lipid interactions in synaptic targeting.